Abstract Despite the clinical success of antiretroviral therapy (ART), more people contract human immunodeficiency virus (HIV) infection daily than initiate ART. Since its inception in 2011, the Martin Delaney Collaboratory program has made important advances towards a cure for HIV, a much-needed effort to comprehensively combat the AIDS pandemic. The 2016 scientific agenda of the Collaboratory of AIDS Researchers for Eradication (CARE) seeks to more rapidly advance approaches for latency disruption and clearance into clinical testing. We hypothesize that the latent state of HIV can be reversed such that antigenic viral proteins are expressed, and that this intervention must be strategically combined with immunotherapies to allow the clearance of cells emerging from latency. Effective implementation of this strategy is expected to lead to the eradication of persistent HIV infection, a cure for AIDS. Our group now possesses substantial expertise previously not brought to bear on this problem, including the skills and tools of an expanded group of pharmaceutical partners. Our initial efforts will focus on the key objectives to facilitate clinical trials of eradication therapy: Detection of HIV antigen-positive cells (IRF I), Clearance of HIV antigen-positive cells (IRF II), Revealing and Clearing Unseen HIV (IRF 3). We envision an iterative process with insights gained in ex vivo, pre-clinical and clinical experiments carried forward to enhance the next step in clinical development and, importantly, fed back to scientists to refine their work, validate assays or hypotheses, and explore new directions. We are dedicated to working together in a nimble program, able to alter the course of our research as directed by our discoveries, convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection.